Clinical outcomes for unprotected left main coronary artery (ULMCA) disease between coronary artery bypass grafting (CABG) and drug-eluting stents (DESs) remain controversial. We aimed to compare the safety and efficacy of percutaneous coronary intervention (PCI) using DESs with CABG in patients with ULMCA disease. Databases were searched for clinical studies that reported outcomes after PCI with DESs and CABG for treatment of ULMCA disease. End points of this meta-analysis were mortality; composite of death, myocardial infarction (MI), or stroke; and target vessel revascularization at 1-year follow-up. Pooled effects were calculated using fixed-effects model (Mantel-Haenszel method) or random-effects models (Dersimonian-Laird method). Twelve clinical studies (3 randomized trials and 9 observational studies) with 5,079 patients were involved in this study. At 1-year follow-up, there were trends toward lower risk of death (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.45 to 1.02) and the composite end point of death, MI, or stroke (OR 0.70, 95% CI 0.49 to 1.00) in the DES group compared to the CABG group. However, target vessel revascularization was significantly higher in the DES group compared to the CABG group (OR 3.52, 95% CI 2.72 to 4.56). In conclusion, PCI with DESs is associated with favorable outcomes for mortality; composite end point of death, MI, or stroke; and a higher risk of target vessel revascularization compared to CABG in patients with ULMCA disease.